The primary goal of this study is to examine the role of viral integration and plasmids in Alzheimer's disease and the process of aging and senescence. Recent development of techniques to detect chromosomally integrated viral geneomes had encouraged us to apply these methodologies to investigate human diseases. The possibility of an association between a viral genome integrated into the chromosome and the occurrence of diseases inherited in a dominant manner, such as familial Alzheimer's disease, is currently being examined. Integration of viral related nucleotide sequences in the genomic DNA of man is being studied using fibroblast cell lines established from individuals belonging to a family with histologically confirmed Alzheimer's disease. Tissues from this Alzheimer pedigree are also being utilized along with tissues obtained from young and aged normal individuals to examine amplification and excision events in the mitochondrial genome as a function of the aging. Since excision can result in the synthesis of circularized mitochondrial plasmids, (the major factor in senescence of some fungal strains) experiments are being conducted to screen for these free mitochondrial plasmids and an attempt is being made to determine their relationship with the state of senescence.